摘要
免疫抑制治疗是成功肾移植的基石。常用的免疫抑制剂环孢菌素,他克莫司、雷帕霉素和霉酚酸。这些药物有狭窄的治疗指数,显示出较高的药代动力学变异性。为了保持有效性和安全性之间的平衡,给药是基于测得的药物浓度。正确的识别,量化和理解测量浓度的变化的来源,促进常规剂量调整在临床实践中。经典的药代动力学研究有限的使用在移植的患者占设计与激烈的采样在一个小的,相对均匀的人口,并确定每项研究中只有单一的变异因子。人口方法是一个强大的工具,用于分析稀疏数据,确定影响药物的药代动力学和估计变异的因素。本报告回顾了群体药动学模型可用环孢素,他克莫司,西罗莫司和成人肾移植患者霉酚酸。主要重点是描述各种人口因素,生化指标,代谢酶和转运蛋白和药物相互作用的遗传多态性,这已被确定为肾移植患者的药代动力学变异的一个重要关注。
关键词: 环孢素、他克莫司、雷帕霉素,霉酚酸,变异性,药代动力学因素,肾移植患者,人口模型。
Current Medicinal Chemistry
Title:Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients
Volume: 23 Issue: 19
Author(s): Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic, Iztok Grabnar
Affiliation:
关键词: 环孢素、他克莫司、雷帕霉素,霉酚酸,变异性,药代动力学因素,肾移植患者,人口模型。
摘要: Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.
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Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic, Iztok Grabnar , Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients, Current Medicinal Chemistry 2016; 23 (19) . https://dx.doi.org/10.2174/0929867323666151221150214
DOI https://dx.doi.org/10.2174/0929867323666151221150214 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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